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Biomedical subjects

Yoshiaki Kajiyama

Publications and source records attributed to Yoshiaki Kajiyama.

12 recordsLinked to original sources
PubMed2006

Alvocidib (Flavopiridol) suppresses tumor growth in SCID mice with human esophageal cancer xenografts without inducing apoptosis.

Alvocidib (Flavopiridol, HMR1275) is a potent inhibitor of multiple cyclin-dependent kinases and has been identified recently as an antitumor agent in several cancers. Previous studies have shown that alvocidib could potentially treat esophageal cancer in vitro. This study evaluates alvocidib for its ability to suppress tumor growth in severe combined immunodeficiency (SCID) mice bearing TE8 human esophageal squamous cell carcinoma (SCC) xenografts. Alvocidib treatment of 10mg/kg body weight reduced tumor volume significantly. Immunohistochemistry analysis of alvocidib-treated tumor sections showed significant reductions in cyclin D1, VEGF, and Rb levels. Alvocidib treatment did not cause a marked increase in apoptotic tumor cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis, yet hematoxylin and eosin staining revealed tumor necrosis. In vivo investigation of alvocidib treatment confirmed antitumor activity in TE8 esophageal xenografts. These findings suggest that alvocidib could be a useful anti-cancer agent for esophageal cancer.

Animals↗
PubMed2005

Monoclonal antibody to HER-2/neu receptor enhances radiosensitivity of esophageal cancer cell lines expressing HER-2/neu oncoprotein.

PURPOSE: The role of HER-2/neu in the response of esophageal cancer to radiation is not well known. The purpose of this study was to evaluate the effect of an anti-HER-2/neu antibody trastuzumab on the proliferation, cell cycle distribution, and radiosensitivity of esophageal cancer cell lines. EXPERIMENTAL DESIGN: Expression of HER-2/neu protein by four esophageal squamous cancer cell lines (KE4, TE8, TE9, and TE10) and an esophageal adenocarcinoma cell line (SKGT4) was assessed using immunohistochemical (IHC) analysis and flow cytometry. We also evaluated HER-2/neu oncogene expression by fluorescence in situ hybridization. As a control for HER-2/neu protein expression and gene amplification, breast cancer cell lines (MCF7, MDA MB175VII, and SKBR3) were also examined. The cytotoxity of trastuzumab (0.1-200 microg/mL) was estimated by the MTT assay, and the cell cycle distribution was determined by flow cytometry. The effect of 10 microg/mL trastuzumab combined with radiation was assessed by a clonogenic assay. RESULTS: Flow cytometry and IHC revealed that two esophageal cancer cell lines (TE9 and SKGT4) showed HER-2/neu expression (IHC 1+ and mean fluorescence intensity of 11-20), while the other esophageal cancer cell lines were negative for HER-2/neu expression. Although trastuzumab alone had no effect on the esophageal cancer cell lines, the combination of 10 microg/mL trastuzumab with radiation showed a synergistic effect on the HER-2/neu expressing cell lines. CONCLUSIONS: This study suggested that trastuzumab plus irradiation may be effective for the treatment of esophageal cancers, including adenocarcinoma and squamous cell cancer with HER-2/neu expression.

Antibodies, Monoclonal↗
PubMed2005

Gastrointestinal stromal tumor in a child and review of the literature.

Gastrointestinal stromal tumors (GIST) are c-KIT positive neoplasm that occur predominantly in adults. A 13-year-old boy who presented with massive gastrointestinal hemorrhage was subsequently diagnosed with GIST of the stomach. The tumor originated from the lesser curvature with a narrow base and no infiltration into surrounding organs. Two metastatic lesions in the liver were also found. Total excision of the gastric lesion was performed followed by adjuvant imatinib mesylate chemotherapy. He has had no signs of recurrence during 8 months of follow-up. GIST in children are rare and their behavior is notoriously difficult to predict. We report our experience and review the literature.

Adolescent↗
PubMed2005

[Esophageal cancer surgery; importance of surgical quality control].

In esophageal cancer, the rate of lymphatic metastasis is higher than any other gastrointestinal cancer. The morbidity and mortality rate of esophageal surgery is still high. In order to reduce high morbidity and mortality rate, esophageal cancer surgery is recommended to be performed at a high-volume hospital in Europe and United States. In Japan, "3-field lymph nodes dissection surgery" has been established for complete lymphatic clearance, and the overall survival has improved. This surgical procedure is now recognized as a standard surgery for advanced esophageal cancer by "Japan Esophageal Society". However, even in Japan, the morbidity and mortality rate of esophageal cancer surgery is higher than gastric or colonic cancer surgery. For rationale of esophageal cancer surgery, we have to continue to improve our surgical quality such as preserving bronchial artery or pulmonary branches of the vagal nerve.

Adenocarcinoma↗
PubMed2004

Loss of heterozygosity analysis shows monoclonal evolution with frequent genetic progression and divergence in esophageal carcinosarcoma.

Carcinosarcoma (spindle cell carcinoma) of the esophagus is a rare neoplasm that shows squamous cell carcinoma (SCC) with a variable component of spindle cell sarcoma. Clinical and pathologic features of this neoplasm have been well documented, but the histogenesis has long been a matter of speculation and dispute. In an attempt to clarify the clonality and genetic relationships in the evolution of this neoplasm, we microdissected a total of 36 carcinomatous and sarcomatous foci from six esophageal carcinosarcoma (CS) and analyzed the allelic status with 25 microsatellite markers on chromosomal arms 3p, 5q, 6q, 8p, 9p, 11q, 13q, 17p, and 18q. In all cases, we found multiple and homogenous allelic losses in both the carcinomatous and sarcomatous components, strongly supporting the concept of monoclonal origin for this neoplasm. Homogeneous allelic losses were detected most frequently on 17p (5 cases), a chromosomal arm that included the p53 locus, followed by 3p, 11q, and 13q (3 cases); 9p (2 cases); and 8p and 18q (1 case). Moreover, five of the six cases showed additional or divergent allelic losses at more than one chromosomal locus at some of the microdissected foci, indicating genetic progression (2 cases) or genetic progression and divergence (3 cases). In four cases, the genetic changes indicated that an original clone of a pure SCC apparently acquired carcinosarcomatous or sarcomatous phenotype by successive genetic changes. On the other hand, we saw no evidence for tumors in which a sarcoma appeared to give rise to a carcinosarcomatous or carcinomatous subclone in the examined cases. In conclusion, our data support the concept that esophageal CS is derived from a single clone originating from a SCC. Furthermore, we showed genetic heterogeneity to accompany the phenotypic divergence, with patterns of genetic alterations that are consistent with both progression and divergence within individual tumors.

Adult↗
PubMed2003

c-erbB-2 oncoprotein expression related to chemoradioresistance in esophageal squamous cell carcinoma.

PURPOSE: Esophageal carcinoma is a challenging target for radiotherapy. To improve treatment efficacy, an investigation of a predictive factor is desirable. In this study, we evaluated the significance of apoptosis and immunohistochemical staining for p53, Ki-67, c-erbB-2 (HER-2/neu), Ku (p70/p80), and DNA-PKcs for predictive markers of the responsiveness to chemoradiotherapy in esophageal squamous cell carcinoma. MATERIALS AND METHODS: This retrospective analysis consisted of 34 patients with esophageal squamous cell carcinoma in whom tumor biopsy was performed before treatment. They were divided into chemoradiosensitive (n = 13) and chemoradioresistant (n = 21) groups according to the tumor response evaluated at a total radiation dose of 40 Gy. The biopsy samples were examined with immunohistochemical staining for various factors and with an in situ nick end labeling method for apoptosis. The examined data were compared between the two groups. RESULTS: The difference in the Ki-67, p53, Ku (p70/p80), DNA-PKcs labeling indexes and the apoptosis index in tumor cells between the chemoradiosensitive and chemoradioresistant groups was not statistically significant. The expression of c-erbB-2 oncoprotein was statistically significant in the chemoradioresistant group (p = 0.02), although it did not correlate with survival. CONCLUSIONS: c-erbB-2 immunostaining is useful for the prediction of chemoradioresistance in esophageal squamous cell carcinoma.

Adult↗
PubMed2003

[Controversies in esophageal cancer surgery].

In esophageal cancer treatment, the choice of treatment modality and the indications and extent of lymph node dissection surgery are controversial. In terms of the biological characteristics, esophageal cancer is more virulent than any other gastrointestinal malignancy. The distribution of lymph node metastases is very wide, extending from the neck to abdominal regions, and the sizes of lymph node metastases are very small. Almost two-thirds of all metastatic lymph nodes showed minute metastases less than 5 mm in diameter. In patients with superficial cancer with only submucosal invasion, lymph nodes metastases were found in both the upper mediastinal and paracardial areas in up to 27% cases. Furthermore, the accuracy of preoperative diagnosis of lymph node metastasis in esophageal cancer is still unsatisfactory. False negative rates in preoperative diagnosis of lymph node metastases are 14% in the neck area, 36% in the mediastinal area, and 34% in the abdominal area. Therefore, in order to cure esophageal cancer by surgery, wide, precise and complete removal of possible metastatic lymph nodes is essential. It is at this time that the quality assurance of surgery is indispensable in reducing morbidity and mortality, and in improving the patient survival. Because both surgery and chemoradiotherapy are local treatments, we must recognize the limitation of these therapeutic modalities. To improve overall survival of esophageal cancer patients, we have to make a more concentrated effort toward the systemic control of this disease.

Contraindications↗
PubMed2003

[Surgery for benign submucosal tumors of the esophagus (leiomyoma and hemangioma)].

Among the submucosal tumors of the esophagus, leiomyoma is the most frequently found. Esophageal leiomyoma usually originates from the muscle layer of the esophageal wall and grows spirally around the esophageal axis. In the surgical treatment of leiomyoma, we enucleate the tumor through video-assisted thoracic surgery. When we enucleate leiomyoma, we must be very careful to aviod perforation of the esophageal mucosa. Esophageal hemangioma is a relatively rare disease. The location of this disease is mainly within the submucosal layer, without invading the muscle layer proper. After confirming the localization within the mucosa or submucosa with endoscopic ultrasonography, esophageal hemangioma can be resected safely using the endoscopic mucosal resection technique. In the treatment of benign esophageal submucosal tumors, "informed consent" is as essential as in esophageal cancer surgery. We have no absolute criteria concerning the indications for surgery for benign esophageal submucosal tumors. We must give reasons why the operation is necessary and indicated to the patients. Surgical treatment of esophageal submucosal tumors should be as minimally invasive as possible.

Endosonography↗
PubMed2002

[Esophagectomy with lymph node dissection through right thoracotomy].

In esophageal cancer, the incidence of lymph node metastasis is much higher than that in gastric or colonic cancer. Lymph node metastasis is frequently found along the recurrent laryngeal nerve and around the gastric cardia. The accuracy rate of preoperative diagnosis of lymph node metastasis is up to 80%, in spite of vigorous diagnostic efforts. In Japan, "esophagectomy with 3-field lymph node dissection through a right thoracotomy" is the standard surgery for advanced esophageal cancer. However, based on the "Comprehensive Registry of Esophageal Cancer in Japan," this standard operation does not prevail nationwide. Although, it is difficult to obtain evidence showing the effects of lymph node dissection for ethical reasons, we must continue accurate lymph node dissection with the best surgical techniques to improve patient survival.

Esophageal Neoplasms↗
PubMedDate not supplied

Sealing the thoracic duct with ultrasonic coagulating shears.

BACKGROUND/AIMS: Ultrasonic coagulating shears were developed as an endosurgical device that allows cutting of vessels without ligation. In this study, we obtained basic data on the feasibility of dividing and sealing the thoracic duct by using ultrasonic coagulating shears. METHODOLOGY: We obtained the thoracic duct and the left gastric artery from surgical specimens of 27 patients. After one end of each vessel was sealed using ultrasonic coagulating shears, we recorded the bursting pressure. The sealed ends of the vessels were also examined histopathologically. RESULTS: The mean bursting pressure of the thoracic duct was high enough to support the clinical use of this device, and was significantly higher than that of the left gastric artery (p<0.001). Microscopic examination of the sealed vessels showed that degenerated collagen fibers were more homogeneous and covered a significantly larger area in the thoracic duct than in the left gastric artery (p<0.001). CONCLUSIONS: The present study provides a basis for using ultrasonic coagulating shears to seal the thoracic duct and possibly lymph node dissection.

Electrocoagulation↗